Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor ...Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor cells which are ideal targets for ADCs.In addition,intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I(HLA I)molecules forming tumor-specific peptide/HLA I complexes.KRAS G12 V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy.In this study,we generated two TCR-mimic antibodydrug conjugates(TCRm-ADCs),2E8-MMAE and 2 A5-MMAE,targeting KRAS G12 V/HLAA*0201 complex,which mediated specific antitumor activity in vitro and in vivo without obvious toxicity.Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs,which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.展开更多
Image restoration is often solved by minimizing an energy function consisting of a data-fidelity term and a regularization term.A regularized convex term can usually preserve the image edges well in the restored image...Image restoration is often solved by minimizing an energy function consisting of a data-fidelity term and a regularization term.A regularized convex term can usually preserve the image edges well in the restored image.In this paper,we consider a class of convex and edge-preserving regularization functions,i.e.,multiplicative half-quadratic regularizations,and we use the Newton method to solve the correspondingly reduced systems of nonlinear equations.At each Newton iterate,the preconditioned conjugate gradient method,incorporated with a constraint preconditioner,is employed to solve the structured Newton equation that has a symmetric positive definite coefficient matrix. The eigenvalue bounds of the preconditioned matrix are deliberately derived,which can be used to estimate the convergence speed of the preconditioned conjugate gradient method.We use experimental results to demonstrate that this new approach is efficient, and the effect of image restoration is reasonably well.展开更多
In the present paper, an attempt is made to obtain the degree of approximation of conjugate of functions (signals) belonging to the generalized weighted W(LP, ξ(t)), (p ≥ 1)-class, by using lower triangular matrix o...In the present paper, an attempt is made to obtain the degree of approximation of conjugate of functions (signals) belonging to the generalized weighted W(LP, ξ(t)), (p ≥ 1)-class, by using lower triangular matrix operator of conjugate series of its Fourier series.展开更多
基金supported by the National Key Research and Development Program of China‘Precision Medicine Research’(Grant No.2017YFC0908602)the State Key Program of National Natural Science of China(Grant No.81430081)National Key R&D Program of China(No.2017YFE0102200)。
文摘Limited clinical application of antibody-drug conjugates(ADCs)targeting tumor associated antigens(TAAs)is usually caused by on-target off-tumor side effect.Tumor-specific mutant antigens(TSMAs)only expressed in tumor cells which are ideal targets for ADCs.In addition,intracellular somatic mutant proteins can be presented on the cell surface by human leukocyte antigen class I(HLA I)molecules forming tumor-specific peptide/HLA I complexes.KRAS G12 V mutation frequently occurred in varied cancer and was verified as a promising target for cancer therapy.In this study,we generated two TCR-mimic antibodydrug conjugates(TCRm-ADCs),2E8-MMAE and 2 A5-MMAE,targeting KRAS G12 V/HLAA*0201 complex,which mediated specific antitumor activity in vitro and in vivo without obvious toxicity.Our findings are the first time validate the strategy of TCRm-ADCs targeting intracellular TSMAs,which improves the safety of antibody-based drugs and provides novel strategy for precision medicine in cancer therapy.
基金supported by the National Basic Research Program (No.2005CB321702)the National Outstanding Young Scientist Foundation(No. 10525102)the Specialized Research Grant for High Educational Doctoral Program(Nos. 20090211120011 and LZULL200909),Hong Kong RGC grants and HKBU FRGs
文摘Image restoration is often solved by minimizing an energy function consisting of a data-fidelity term and a regularization term.A regularized convex term can usually preserve the image edges well in the restored image.In this paper,we consider a class of convex and edge-preserving regularization functions,i.e.,multiplicative half-quadratic regularizations,and we use the Newton method to solve the correspondingly reduced systems of nonlinear equations.At each Newton iterate,the preconditioned conjugate gradient method,incorporated with a constraint preconditioner,is employed to solve the structured Newton equation that has a symmetric positive definite coefficient matrix. The eigenvalue bounds of the preconditioned matrix are deliberately derived,which can be used to estimate the convergence speed of the preconditioned conjugate gradient method.We use experimental results to demonstrate that this new approach is efficient, and the effect of image restoration is reasonably well.
文摘In the present paper, an attempt is made to obtain the degree of approximation of conjugate of functions (signals) belonging to the generalized weighted W(LP, ξ(t)), (p ≥ 1)-class, by using lower triangular matrix operator of conjugate series of its Fourier series.
